Amantadine-based combination therapy of Parkinson’s disease to prevent fluctuation and dyskinesia – experiences from a Parkinson outpatient clinic

Background The standard therapy of Parkinson’s disease consists in supplementing the depleted dopamine with oral levodopa. The disadvantages of the levodopa monotherapy – comparable to other dopaminergic substances – are the dose-dependent development of dyskinesia in ON-phases, and bradykinesia and akinesia in OFF-phases, the latter being a sign of dopaminergic deficiency with a recurrence of Parkinson’s symptoms. Aim of the study In order to omit the side effects of levodopa, we devised a combination therapy consisting of amantadine, a monoamine oxidase type B-inhibitor and a dopamine agonist. Levodopa was added at a low dose, if necessary. Methods In a retrospective, monocenter study based on the patient records, we report the long-term results in 132 PD patients who had been treated with the amantadine-based therapy for up to 13 years in an outpatient Parkinson clinic. Results In 132 patients with the amantadine-based combination therapy, the mean UPDRS III score improved by 5.7 points from baseline during the first 2 years of treatment. Over the following 3 years it increased and remained at a plateau level slightly below baseline for the next 5 years. At no time did more than 20% of the patients suffer from Hoehn & Yahr stage 3 or higher. Only seven patients exhibited “OFF” periods and only seven (6 with additional levodopa) presented with dyskinesia at any time during therapy. The most important adverse effect was lower leg edema. Conclusion The combination therapy of amantadine, a monoamine oxidase type B-inhibitor and a dopamine agonist is an alternate therapeutic approach that may be able to prevent dyskinesia and fluctuations by drug pharmacokinetics and synergistic effects, and may postpone or reduce the amount of levodopa. Prospective controlled studies are needed to compare the effects of the amantadine-based combination therapy with the standard levodopa therapy for Parkinson’s disease.